Saudi Cultural Missions Theses & Dissertations
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Item Restricted Evaluation of the Antibacterial, Anti-inflammatory and Wound Healing Properties of Frankincense (Boswellia frereana).(CARDIFF UNIVERSITY, 2025) ALQARNI, ABDULAZIZ; Thomas, ChristopherChronic wounds, already a major clinical and healthcare issue, are expected to grow due to demographic changes, a rise in multi-health conditions, and an increase in conditions like peripheral vascular disease, diabetes, and obesity. Despite such different treatment choices, recurrent deficiencies in wound care have prompted interest in alternate therapy approaches and research over the last few decades. This research investigates the medicinal properties of Boswellia frereana, a tree exudate indigenous to Somaliland (northern Somalia) that is commonly used in traditional medicine. The objective of this study was to investigate it’s potential to treat chronic wounds through studying it’s antibacterial, antibiofilm, anti-inflammatory, and wound healing properties, in vitro. Following extractions, Gas Chromatography-Mass spectrometry (GC-MS) was used to identify the chemical components present in each extracts, alcoholic extracts and essential oils from different suppliers, whilst High Performance Liquid Chromatography (HPLC) was used to quantify the main chemical component, 3-epilupeol, present in the alcoholic extracts. The extracts were evaluated for their Antibacterial effect against the most common bacteria found in chronic wounds (Staphylococcus aureus, Pseudomonas aeruginosa and Methicillin- resistant Staphylococcus aureus) using well diffusion and broth microdilution techniques. The efficacy of B. frereana extracts in inhibiting and eradicating bacterial biofilm was assessed by crystal violet staining and the Live/Dead microbiological viability assay utilising Confocal Laser Scanning Microscopy (CLSM). MTT and scratch wound assays assessed the effects of these extracts on immortalised human skin keratinocytes (HaCaT) and fibroblast cell lines proliferation, migration, and cytotoxicity. Finally, To determining the effects of plant extracts on the production of a panel of inflammatory mediators, LPS-stimulated HaCaT cells were used to assess the anti-inflammatory effects of the extracts. GC-MS analysis identified two chemotypes of B. frereana frankincense, one high in α-Thujene and another high in α-Pinene. HPLC was found to be a more accurate analytical method, than GC-MS, for quantifying the 3-epilupeol content. The essential oil extracts, a-pinene, and b- pinene were all shown to possess significant antibacterial activity against Gram-positive pathogens in both planktonic and biofilm environments. Ethanolic extracts, essential oil, 3- IV epilupeol, and a-pinene induced HaCaT and fibroblast proliferation at low concentrations. However, only oil extracts and a-pinene (0.1 µg/mL) increased the migration of HaCaT cells. The anti-inflammatory study has shown that ethanolic extracts, essential oil, epilupeol, and α- pinene significantly reduced the protein levels of select inflammatory mediators, including IL- 1B, IL-6, IL-8 and TNF-α. This research confirms many reported ethnobotanical applications of frankincense to treat wounds and inflammation.28 0Item Restricted Identification of Antimicrobial Peptides against Gram-negative Bacteria(Saudi Digital Library, 2023-12-20) Alsaab, Fahad; Van Hoek, MoniqueAntibiotic resistance in bacteria has been rising due to excessive and improper use of antibiotics. There is a pressing need to find alternative approaches to tackle this issue. Unconventional antimicrobials have been proposed to combat multidrug resistant (MDR) bacteria. Antimicrobial peptides (AMPs) are promising compounds for fighting bacterial infections. AMPs are a cationic polypeptide chain that can target microorganisms, including bacteria. In this work, three approaches of peptide design have been implemented to generate novel peptides with a focus on gram-negative bacteria. Computational-aided positional analysis method was utilized to generate peptides based on pre-existing dataset of Acinetobacter (A.) baumannii-active peptides to target multidrug resistant (MDR) A. baumannii. The output resulted in the generation of five peptides, HRZN-13 to -17. HRZN-15 peptide had the strongest antibacterial and antibiofilm activity against MDR A. baumannii among HRZN peptides. However, it was toxic to human red blood cells (RBCs) and Galleria mellonella (waxworms). Rational design created a novel sequence GATR-3 from a cryptic peptide that was isolated from American alligator, which we characterized in this study against A. baumannii. GATR-3 exhibited potent antimicrobial activity against a panel of MDR A. baumannii strains. The most exciting finding was that it inhibited biofilm formation as well as eradicated preformed biofilm in this wound-infecting pathogen. GATR-3 did not cause toxicity in hepatocytes, human RBCs and G. mellonella. It also demonstrated host-directed activity, inducing migration of macrophages. The third method that was employed in this study is chemical modification of naturally occurring peptides. The human cathelicidin LL-37 peptide was dissected to find smaller fragments that have antibiofilm activity against Francisella novicida. KR-12 was the smallest fragment tested that exhibited antibiofilm activity but failed to inhibit growth of F. novicida, indicating it’s antibiofilm activity. Therefore, chemical staples were introduced on KR-12 and KR-16 fragments to support their secondary structure conformations and potentially increase their stability or activity. Stapled peptides successfully demonstrated improved growth-inhibitory effect of F. novicida, compared to the native peptides, with minimal toxicity towards human RBCs. All the peptide design methods presented in this dissertation led to the production of novel peptides with activity against gram-negative bacteria.55 0Item Restricted Novel Bioactive Low-Shrinkage-Stress Composite with Antibacterial and Remineralization Properties(Saudi Digital Library, 2023-11-28) Alhussein, Abdullah; Huakun, Xu; Michael, D. Weir; Abraham, Schneider; MaryAnn, Jabra-Rizk; Jirun, SunMethacrylate-based resin composites are frequently employed in dentistry for their aesthetic qualities, durability, and adhesive properties. Nevertheless, these restorations generally exhibit a lifespan of 5 to 10 years, with recurrent caries and tooth fractures being primary failure factors. Marginal integrity and the absence of bioactivity at the tooth-restoration junction contribute to recurrent caries development. Consequently, this dissertation endeavors to introduce a novel bioactive low-shrinkage-stress nanocomposite, featuring dimethylaminododecyl methacrylate (DMADDM) as an antibacterial agent, as well as remineralization nanoparticles of calcium fluoride (nCaF2) and nanoparticles of amorphous calcium phosphate (NACP), with the potential of increase the longevity of dental restoration and protect tooth structure. All novel formulations of low-shrinkage-stress composite were subjected to a series of mechanical, antibacterial, cytocompatibility, and ion release assessments. First, we investigated the optimum concentration of DMADDM that can be incorporated with a low-shrinkage-stress composite without compromising mechanical properties. We found that incorporation of up to 5% DMADDM into a low-shrinkage stress composite efficiently inhibited Streptococcus mutans (S. mutans) biofilm commonly associated with secondary caries. This potent antibacterial effect is achieved while maintaining excellent mechanical properties and minimizing polymerization shrinkage stress, potentially improving the long-term success of dental restorations. Next, we investigated the antibacterial and cytocompatibility of the incorporation of 3% DMADDM with 20% nCaF2 or 20% NCAP into a low-shrinkage-stress nanocomposite. We found that incorporating DMADDM with either nCaF2 or NACP into a low-shrinkage-stress nanocomposite provides a potent antibacterial effect against S. mutans biofilm while maintaining excellent mechanical properties. In addition, the novel formulations demonstrated excellent biocompatibility against human gingival fibroblasts and dental pulp stem cells. Lastly, we investigated the ions release and antibacterial properties against a salivary biofilm for our innovative formulations. The innovative mixture of DMADDM, NACP, and nCaF2 demonstrated strong antibiofilm effects on salivary biofilm, while concomitantly releasing a significant amount of remineralizing ions. This nanocomposite is a promising dental material with antibiofilm and remineralization capacities, with the potential to reduce polymerization-related microleakage and recurrent caries.26 0